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Winheim, E.* ; Santos-Peral, A.* ; Ehm, T.* ; Rinke, L.* ; Riemer, S.* ; Zaucha, M. ; Goresch, S.* ; Lehmann, L.* ; Eisenächer, K.* ; Pritsch, M.* ; Barba-Spaeth, G.* ; Straub, T.* ; Rothenfußer, S. ; Krug, A.B.*

Interferon-induced activation of dendritic cells and monocytes by yellow fever vaccination correlates with early antibody responses.

Proc. Natl. Acad. Sci. U.S.A. 122:e2422236122 (2025)

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Yellow fever vaccination provides long-lasting protection and is a unique model for studying the immune response to an acute RNA virus infection in humans. To elucidate the early innate immune events preceding the rapid generation of protective immunity, we performed transcriptome analysis of human blood dendritic cell (DC) and monocyte subpopulations before and 3, 7, 14, and 28 d after vaccination. We detected temporary upregulation of IFN-stimulated genes (ISG) in all DC and monocyte subsets on days 3 and 7 after vaccination as well as cell type-specific responses and response kinetics. Single-cell RNA sequencing revealed rapid appearance of activated DC and monocyte clusters dominated by ISGs, inflammatory chemokines, and genes involved in antigen processing and presentation. This was confirmed by flow cytometric analysis in a large cohort of vaccinees. We identified SIGLEC1/CD169 upregulation as a sensitive indicator of the transient IFN-induced activation state elicited in DCs and monocytes by YF17D vaccination correlating with early protective IgM antibody responses.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Dendritic Cells ; Interferon ; Monocytes ; Vaccination ; Yellow Fever Virus; Zika Virus-infection; I Interferon; Differentiation; Immunogenicity; Replication; Immunity; Pathways; Subset

ISSN (print) / ISBN 0027-8424

e-ISSN 1091-6490

Journal Proceedings of the National Academy of Sciences of the United States of America

Quellenangaben Volume: 122, Issue: 19, Article Number: e2422236122

Publisher National Academy of Sciences

Publishing Place 2101 Constitution Ave Nw, Washington, Dc 20418 Usa

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Unit for Clinical Pharmacology (KKG-EKLiP)

Grants Agence Nationale de la Recherche (ANR)
French National Research Agency (ANR)
European Union's Horizon Europe research and innovation programme
IMed consortium of the German Helmholtz Societies
Einheit fur Klinische Pharmakologie, Helmholtz Zentrum Munchen, Neuherberg, Germany
Friedrich-Baur-Stiftung
Villigst Foundation

Deutsche Forschungsgemeinschaft (DFG) Project